CH615173A5 - - Google Patents

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Publication number: CH615173A5
Authority: CH; Switzerland
Prior art keywords: formula; parts; lower alkyl; compounds; group
Prior art date: 1974-06-21

Application number

CH809875A

Other languages

German (de)

English (en)

Inventor

Paul Adriaan Jan Janssen

Albert H M Th Van Heertum

Jan Vandenberk

Marcel J M C Van Der Aa

Original Assignee

Janssen Pharmaceutica Nv

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1974-06-21

Filing date

1975-06-20

Publication date

1980-01-15

1975-06-20 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

1980-01-15 Publication of CH615173A5 publication Critical patent/CH615173A5/de

Links

150000001875 compounds Chemical class 0.000 claims description 89
125000000217 alkyl group Chemical group 0.000 claims description 41
238000010992 reflux Methods 0.000 claims description 36
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
238000000034 method Methods 0.000 claims description 29
239000002253 acid Substances 0.000 claims description 28
150000003839 salts Chemical class 0.000 claims description 18
150000002148 esters Chemical group 0.000 claims description 16
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 9
239000002904 solvent Substances 0.000 claims description 8
125000005907 alkyl ester group Chemical group 0.000 claims description 6
125000003386 piperidinyl group Chemical group 0.000 claims description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
239000003513 alkali Substances 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
150000001298 alcohols Chemical class 0.000 claims description 4
239000007858 starting material Substances 0.000 claims description 4
238000007126 N-alkylation reaction Methods 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000005490 tosylate group Chemical group 0.000 claims description 3
SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 2
LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 claims description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical group CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
239000000203 mixture Substances 0.000 description 90
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 61
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 54
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 46
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 32
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 31
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
239000000047 product Substances 0.000 description 30
239000011541 reaction mixture Substances 0.000 description 30
229960001701 chloroform Drugs 0.000 description 28
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 27
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 26
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 26
229910000029 sodium carbonate Inorganic materials 0.000 description 26
-1 phenyl radicals Chemical class 0.000 description 25
238000001816 cooling Methods 0.000 description 21
239000000706 filtrate Substances 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 19
239000010410 layer Substances 0.000 description 19
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
239000003054 catalyst Substances 0.000 description 14
238000004440 column chromatography Methods 0.000 description 12
239000003480 eluent Substances 0.000 description 12
239000000741 silica gel Substances 0.000 description 12
229910002027 silica gel Inorganic materials 0.000 description 12
239000012485 toluene extract Substances 0.000 description 12
150000003254 radicals Chemical class 0.000 description 11
239000012044 organic layer Substances 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
150000004702 methyl esters Chemical class 0.000 description 9
UXXLTPGCINZEFM-UHFFFAOYSA-N 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene Chemical compound C1=CC(F)=CC=C1C(CCCCl)C1=CC=C(F)C=C1 UXXLTPGCINZEFM-UHFFFAOYSA-N 0.000 description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
239000000284 extract Substances 0.000 description 8
239000001257 hydrogen Substances 0.000 description 8
239000000543 intermediate Substances 0.000 description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 7
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
238000003756 stirring Methods 0.000 description 7
239000008096 xylene Substances 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
239000012071 phase Substances 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
MQISNDAUWVHJML-UHFFFAOYSA-N 1-butyl-4-fluorobenzene Chemical compound CCCCC1=CC=C(F)C=C1 MQISNDAUWVHJML-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
239000007868 Raney catalyst Substances 0.000 description 5
229910000564 Raney nickel Inorganic materials 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
235000011114 ammonium hydroxide Nutrition 0.000 description 5
239000002585 base Substances 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 5
239000012458 free base Substances 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
239000005909 Kieselgur Substances 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
239000004202 carbamide Substances 0.000 description 4
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 4
SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical class C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 3
RZKKOBGFCAHLCZ-UHFFFAOYSA-N 1,4-dichloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1Cl RZKKOBGFCAHLCZ-UHFFFAOYSA-N 0.000 description 3
VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 3
DOAYWDKFDPSTSV-UHFFFAOYSA-N 5-chloro-1,3-dihydro-1-(4-piperidinyl)-2h-benzimidazol-2-one Chemical compound O=C1NC2=CC(Cl)=CC=C2N1C1CCNCC1 DOAYWDKFDPSTSV-UHFFFAOYSA-N 0.000 description 3
241000282472 Canis lupus familiaris Species 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
150000001721 carbon Chemical group 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
125000004494 ethyl ester group Chemical group 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000007787 solid Substances 0.000 description 3
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
VLVNHMVSVDVAOA-UHFFFAOYSA-N 1,5-dichloro-2-nitro-4-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=C(Cl)C=C1Cl VLVNHMVSVDVAOA-UHFFFAOYSA-N 0.000 description 2
TZGFQIXRVUHDLE-UHFFFAOYSA-N 1-chloro-2-nitro-4-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1Cl TZGFQIXRVUHDLE-UHFFFAOYSA-N 0.000 description 2
WZVBIHCNOIJOBW-UHFFFAOYSA-N 4-chloro-3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound C1=2C(Cl)=CC=CC=2NC(=O)N1C1CCNCC1 WZVBIHCNOIJOBW-UHFFFAOYSA-N 0.000 description 2
HLVGSAJSPZQLEX-UHFFFAOYSA-N 5-chloro-3-(2-methylpiperidin-4-yl)-6-(trifluoromethyl)-1h-benzimidazol-2-one Chemical compound C1CNC(C)CC1N1C(=O)NC2=CC(C(F)(F)F)=C(Cl)C=C21 HLVGSAJSPZQLEX-UHFFFAOYSA-N 0.000 description 2
ODHZAPGRXOUGQA-UHFFFAOYSA-N 5-chloro-3-methyl-1-piperidin-4-ylbenzimidazol-2-one Chemical compound O=C1N(C)C2=CC(Cl)=CC=C2N1C1CCNCC1 ODHZAPGRXOUGQA-UHFFFAOYSA-N 0.000 description 2
DVGDFQDLSRUUCL-UHFFFAOYSA-N 5-chloro-3-piperidin-4-yl-6-(trifluoromethyl)-1h-benzimidazol-2-one Chemical compound C1=2C=C(Cl)C(C(F)(F)F)=CC=2NC(=O)N1C1CCNCC1 DVGDFQDLSRUUCL-UHFFFAOYSA-N 0.000 description 2
CPPROPWJNRGALK-UHFFFAOYSA-N 6-bromo-3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC(Br)=CC=C2N1C1CCNCC1 CPPROPWJNRGALK-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
206010047700 Vomiting Diseases 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 2
229960004046 apomorphine Drugs 0.000 description 2
MYONAGGJKCJOBT-UHFFFAOYSA-N benzimidazol-2-one Chemical compound C1=CC=CC2=NC(=O)N=C21 MYONAGGJKCJOBT-UHFFFAOYSA-N 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000000605 extraction Methods 0.000 description 2
150000008282 halocarbons Chemical class 0.000 description 2
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
239000005457 ice water Substances 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
230000005923 long-lasting effect Effects 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000004570 mortar (masonry) Substances 0.000 description 2
230000000701 neuroleptic effect Effects 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
235000006408 oxalic acid Nutrition 0.000 description 2
YVUQSNJEYSNKRX-UHFFFAOYSA-N pimozide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCC(N2C(NC3=CC=CC=C32)=O)CC1 YVUQSNJEYSNKRX-UHFFFAOYSA-N 0.000 description 2
229960003634 pimozide Drugs 0.000 description 2
BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
238000011282 treatment Methods 0.000 description 2
230000008673 vomiting Effects 0.000 description 2
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
QEHULDSDCDEOFP-UHFFFAOYSA-N 1-[1-[4,4-bis(4-fluorophenyl)butyl]piperidin-4-yl]-5-chloro-3-methylbenzimidazol-2-one Chemical compound O=C1N(C)C2=CC(Cl)=CC=C2N1C(CC1)CCN1CCCC(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 QEHULDSDCDEOFP-UHFFFAOYSA-N 0.000 description 1
XXFUZSHTIOFGNV-UHFFFAOYSA-N 1-bromoprop-1-yne Chemical compound CC#CBr XXFUZSHTIOFGNV-UHFFFAOYSA-N 0.000 description 1
WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical compound [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 description 1
BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical class [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 description 1
WHNAMGUAXHGCHH-UHFFFAOYSA-N 1-nitro-3-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=CC(C(F)(F)F)=C1 WHNAMGUAXHGCHH-UHFFFAOYSA-N 0.000 description 1
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
VGRCFVMVLQILNL-UHFFFAOYSA-N 3-(2-methylpiperidin-4-yl)-6-(trifluoromethyl)-1h-benzimidazol-2-one Chemical compound C1CNC(C)CC1N1C(=O)NC2=CC(C(F)(F)F)=CC=C21 VGRCFVMVLQILNL-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
QQVBGXPVJDLGDB-UHFFFAOYSA-N 3-benzyl-5-chloro-1-piperidin-4-ylbenzimidazol-2-one Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(Cl)=CC=C2N1C1CCNCC1 QQVBGXPVJDLGDB-UHFFFAOYSA-N 0.000 description 1
BUUABGYZBONSRS-UHFFFAOYSA-N 3-o-ethyl 1-o-methyl 2-methyl-4-oxopiperidine-1,3-dicarboxylate Chemical compound CCOC(=O)C1C(C)N(C(=O)OC)CCC1=O BUUABGYZBONSRS-UHFFFAOYSA-N 0.000 description 1
BYNBAMHAURJNTR-UHFFFAOYSA-N 3-piperidin-4-yl-1h-benzimidazol-2-one Chemical class O=C1NC2=CC=CC=C2N1C1CCNCC1 BYNBAMHAURJNTR-UHFFFAOYSA-N 0.000 description 1
WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
WRFYIYOXJWKONR-UHFFFAOYSA-N 4-bromo-2-methoxyaniline Chemical compound COC1=CC(Br)=CC=C1N WRFYIYOXJWKONR-UHFFFAOYSA-N 0.000 description 1
WVYWICLMDOOCFB-UHFFFAOYSA-N 4-methyl-2-pentanol Chemical compound CC(C)CC(C)O WVYWICLMDOOCFB-UHFFFAOYSA-N 0.000 description 1
UBANYIIUQXCNNW-UHFFFAOYSA-N 5,6-dichloro-3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound C1=2C=C(Cl)C(Cl)=CC=2NC(=O)N1C1CCNCC1 UBANYIIUQXCNNW-UHFFFAOYSA-N 0.000 description 1
JLPGIAYXVKNEQN-UHFFFAOYSA-N 5-chloro-3-(2-oxopropyl)-1-piperidin-4-ylbenzimidazol-2-one;hydrochloride Chemical compound Cl.O=C1N(CC(=O)C)C2=CC(Cl)=CC=C2N1C1CCNCC1 JLPGIAYXVKNEQN-UHFFFAOYSA-N 0.000 description 1
SFDZOBSBMNCJJX-UHFFFAOYSA-N 5-chloro-4-methyl-3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound C1=2C(C)=C(Cl)C=CC=2NC(=O)N1C1CCNCC1 SFDZOBSBMNCJJX-UHFFFAOYSA-N 0.000 description 1
QVPKVYJAOUYXJC-UHFFFAOYSA-N 6-chloro-3-(2-methylpiperidin-4-yl)-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.C1CNC(C)CC1N1C(=O)NC2=CC(Cl)=CC=C21 QVPKVYJAOUYXJC-UHFFFAOYSA-N 0.000 description 1
SZRACBYENLZHLD-UHFFFAOYSA-N 6-chloro-3-(3-methylpiperidin-4-yl)-1h-benzimidazol-2-one Chemical compound CC1CNCCC1N1C(=O)NC2=CC(Cl)=CC=C21 SZRACBYENLZHLD-UHFFFAOYSA-N 0.000 description 1
QXPKJUZDMPPKPR-UHFFFAOYSA-N 6-fluoro-3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC(F)=CC=C2N1C1CCNCC1 QXPKJUZDMPPKPR-UHFFFAOYSA-N 0.000 description 1
YSPOBZJVVYXUBQ-UHFFFAOYSA-N 6-iodo-3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC(I)=CC=C2N1C1CCNCC1 YSPOBZJVVYXUBQ-UHFFFAOYSA-N 0.000 description 1
AWSJFOUAEDCEGT-UHFFFAOYSA-N 6-methyl-3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC(C)=CC=C2N1C1CCNCC1 AWSJFOUAEDCEGT-UHFFFAOYSA-N 0.000 description 1
IVGOGCAUCUCWSL-UHFFFAOYSA-N C(C)C(C=C)C(=O)O.C(C=C)(=O)OCC Chemical compound C(C)C(C=C)C(=O)O.C(C=C)(=O)OCC IVGOGCAUCUCWSL-UHFFFAOYSA-N 0.000 description 1
HNUALPPJLMYHDK-UHFFFAOYSA-N C[CH]C Chemical compound C[CH]C HNUALPPJLMYHDK-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 1
229910001516 alkali metal iodide Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910001619 alkaline earth metal iodide Inorganic materials 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
125000004848 alkoxyethyl group Chemical group 0.000 description 1
125000004448 alkyl carbonyl group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229960004909 aminosalicylic acid Drugs 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
LPHJNLVMFDNLIH-UHFFFAOYSA-N azanium;methane;hydroxide Chemical compound C.N.O LPHJNLVMFDNLIH-UHFFFAOYSA-N 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
238000005574 benzylation reaction Methods 0.000 description 1
NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
JENQQNDKUFOZAO-UHFFFAOYSA-N ethyl 3-(benzylamino)butanoate Chemical compound CCOC(=O)CC(C)NCC1=CC=CC=C1 JENQQNDKUFOZAO-UHFFFAOYSA-N 0.000 description 1
BEBFRFMLVIJOSE-UHFFFAOYSA-N ethyl 4-(5-chloro-2-oxo-3h-benzimidazol-1-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1N1C(=O)NC2=CC(Cl)=CC=C21 BEBFRFMLVIJOSE-UHFFFAOYSA-N 0.000 description 1
LFERNNOIIBIQFB-UHFFFAOYSA-N ethyl 4-(5-chloro-3-methyl-2-oxobenzimidazol-1-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1N1C(=O)N(C)C2=CC(Cl)=CC=C21 LFERNNOIIBIQFB-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
YSPVHAUJXLGZHP-UHFFFAOYSA-N ethyl piperidine-1-carboxylate Chemical compound CCOC(=O)N1CCCCC1 YSPVHAUJXLGZHP-UHFFFAOYSA-N 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
238000011866 long-term treatment Methods 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
HOCBEMINAPCXII-UHFFFAOYSA-N methyl 2-methyl-4-oxopiperidine-1-carboxylate Chemical compound COC(=O)N1CCC(=O)CC1C HOCBEMINAPCXII-UHFFFAOYSA-N 0.000 description 1
AXCCWWCQXOPDNI-UHFFFAOYSA-N methyl 4-(2-amino-4-chloroanilino)-3-methylpiperidine-1-carboxylate Chemical compound CC1CN(C(=O)OC)CCC1NC1=CC=C(Cl)C=C1N AXCCWWCQXOPDNI-UHFFFAOYSA-N 0.000 description 1
OTWOWALJPFXZDK-UHFFFAOYSA-N methyl 4-(4-chloro-2-nitroanilino)-2-methylpiperidine-1-carboxylate Chemical compound C1C(C)N(C(=O)OC)CCC1NC1=CC=C(Cl)C=C1[N+]([O-])=O OTWOWALJPFXZDK-UHFFFAOYSA-N 0.000 description 1
DZOXVSMMUMQCPA-UHFFFAOYSA-N methyl 4-(4-chloro-2-nitroanilino)-3-methylpiperidine-1-carboxylate Chemical compound CC1CN(C(=O)OC)CCC1NC1=CC=C(Cl)C=C1[N+]([O-])=O DZOXVSMMUMQCPA-UHFFFAOYSA-N 0.000 description 1
IBRFTLWBPMFTCW-UHFFFAOYSA-N methyl 4-(5-chloro-2-oxo-3h-benzimidazol-1-yl)-3-methylpiperidine-1-carboxylate Chemical compound CC1CN(C(=O)OC)CCC1N1C(=O)NC2=CC(Cl)=CC=C21 IBRFTLWBPMFTCW-UHFFFAOYSA-N 0.000 description 1
GZYJYLZCWUNOSI-UHFFFAOYSA-N methyl 4-[(6-amino-6-chlorocyclohexa-2,4-dien-1-yl)amino]-2-methylpiperidine-1-carboxylate Chemical compound NC1(C(C=CC=C1)NC1CC(N(CC1)C(=O)OC)C)Cl GZYJYLZCWUNOSI-UHFFFAOYSA-N 0.000 description 1
XNADZBOFGCTACU-UHFFFAOYSA-N methyl 4-amino-2-methylpiperidine-1-carboxylate Chemical compound COC(=O)N1CCC(N)CC1C XNADZBOFGCTACU-UHFFFAOYSA-N 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
MNRGFUBMMILKAL-UHFFFAOYSA-N methyl phenylmethanesulfonate Chemical group COS(=O)(=O)CC1=CC=CC=C1 MNRGFUBMMILKAL-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
LKRMTUUCKBQGFO-UHFFFAOYSA-N n-phenylpiperidin-4-amine Chemical compound C1CNCCC1NC1=CC=CC=C1 LKRMTUUCKBQGFO-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical class O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/76—Chemiluminescence; Bioluminescence
- G01N21/766—Chemiluminescence; Bioluminescence of gases
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N31/00—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N31/00—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
- G01N31/10—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods using catalysis
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/17—Nitrogen containing
- Y10T436/173845—Amine and quaternary ammonium
- Y10T436/175383—Ammonia
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/17—Nitrogen containing
- Y10T436/177692—Oxides of nitrogen
- Y10T436/178459—Only nitrogen dioxide

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Physics & Mathematics (AREA)
General Health & Medical Sciences (AREA)
Immunology (AREA)
Analytical Chemistry (AREA)
Pathology (AREA)
General Physics & Mathematics (AREA)
Biochemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Molecular Biology (AREA)
Engineering & Computer Science (AREA)
Plasma & Fusion (AREA)
Neurology (AREA)
Anesthesiology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Neurosurgery (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Biomedical Technology (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)

CH809875A 1974-06-21 1975-06-20 CH615173A5 (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US05/481,594 US3989707A (en)	1974-06-21	1974-06-21	Benzimidazolinone derivatives

Publications (1)

Publication Number	Publication Date
CH615173A5 true CH615173A5 (fr)	1980-01-15

Family

ID=23912586

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH809875A CH615173A5 (fr)	1974-06-21	1975-06-20

Country Status (25)

Country	Link
US (1)	US3989707A (fr)
JP (1)	JPS5840553B2 (fr)
AT (1)	AT345833B (fr)
AU (1)	AU500910B2 (fr)
BE (1)	BE830403A (fr)
CA (1)	CA1053235A (fr)
CH (1)	CH615173A5 (fr)
CS (1)	CS190480B2 (fr)
DE (1)	DE2527261C2 (fr)
DK (1)	DK141751B (fr)
ES (1)	ES438714A1 (fr)
FI (1)	FI59589C (fr)
FR (1)	FR2275210A1 (fr)
GB (1)	GB1505173A (fr)
HU (1)	HU170435B (fr)
IE (1)	IE41383B1 (fr)
IL (1)	IL47529A (fr)
NL (1)	NL180587C (fr)
NO (1)	NO142400C (fr)
PH (1)	PH13604A (fr)
PL (1)	PL98220B1 (fr)
SE (2)	SE416298B (fr)
SU (1)	SU585811A3 (fr)
YU (1)	YU159475A (fr)
ZA (1)	ZA753968B (fr)

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US4066772A (en) *	1975-07-21	1978-01-03	Janssen Pharmaceutica N.V.	1,3-Dihydro-1-[3-(1-piperidinyl)propyl]-2H-benzimidazol-2-ones and related compounds
NZ181256A (en) *	1975-07-21	1978-04-28	Janssen Pharmaceutica Nv	1-(w-benzazol-11-ylalkyl)-piperidine derivatives and pharmaceutical compositions containing certain of these derivatives
US4076821A (en) *	1976-02-27	1978-02-28	Yoshitomi Pharmaceutical Industries, Ltd.	4,4-Diphenylcycloalkylpiperidines and psychotropic compositions thereof
US4219559A (en) *	1979-01-10	1980-08-26	Janssen Pharmaceutica N.V.	N-Heterocyclyl-4-piperidinamines
MA19091A1 (fr) *	1980-03-10	1981-10-01	Janssen Pharmaceutica Nv	Nouveaux derives de i-(4-aryl-cyclohexyl)piperidine .
US4777265A (en) *	1986-03-11	1988-10-11	Basf Aktiengesellschaft	Preparation of acrylates and methacrylates
DE4107857A1 (de) *	1991-03-12	1992-09-17	Thomae Gmbh Dr K	Cyclische harnstoffderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
AU2388697A (en)	1996-04-19	1997-11-12	Neurosearch A/S	1-(4-piperidyl)-benzimidazoles having neurotrophic activity
DE69826278T2 (de) *	1997-05-30	2005-11-10	Banyu Pharmaceutical Co., Ltd.	2-oxoimidazol-derivate
WO2000031061A1 (fr) *	1998-11-20	2000-06-02	Banyu Pharmaceutical Co., Ltd.	Derives de 2-oxo-imidazole
EP1196391A1 (fr) *	1999-07-21	2002-04-17	Fujisawa Pharmaceutical Co., Ltd.	Derives de benzimidazolone et leur utilisation comme inhibiteurs de la phosphodiesterase
EP1451173A4 (fr) *	2001-11-01	2005-10-26	Icagen Inc	Piperidines
EP1937670A1 (fr) *	2005-09-30	2008-07-02	Glaxo Group Limited	Benzimidazolones exerçant une activite au niveau du recepteur m1
ES2391107T3 (es) *	2005-09-30	2012-11-21	Glaxo Group Limited	Compuestos que tienen actividad en el receptor M1 y sus usos en medicina
KR20130091791A (ko) *	2005-09-30	2013-08-19	글락소 그룹 리미티드	Ｍ１ 수용체에서 활성을 갖는 화합물 및 그의 의약적 용도
GB0605784D0 (en) *	2006-03-22	2006-05-03	Glaxo Group Ltd	Compounds
EP1997381A1 (fr) *	2007-06-01	2008-12-03	Commissariat à l'Energie Atomique	Utilisation d'un composant ayant une activité inhibitrice de synthase de monogalactosyldiacylglycerol en tant qu'herbicide ou algicide, compositions herbicides et algicides
GB0718415D0 (en) *	2007-09-20	2007-10-31	Glaxo Group Ltd	Compounds
MX2012001875A (es) *	2009-08-12	2012-07-20	Janssen Pharmaceutica Nv	Proceso para la preparación de inhibidores de la catepsina s.
US20240287019A1 (en) *	2021-06-07	2024-08-29	Kinki University	T-type calcium channel blocker

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE633495A (fr) *	1962-06-13
US3161645A (en) *	1962-12-18	1964-12-15	Res Lab Dr C Janssen N V	1-(1-aroylpropyl-4-piperidyl)-2-benzimidazolinones and related compounds
BE659364A (fr) *	1964-02-05
US3799932A (en) *	1970-03-20	1974-03-26	Sumitomo Chemical Co	Gamma-piperidinobutyrophenones
JPS5511671B2 (fr) *	1971-08-26	1980-03-26

1974
- 1974-06-21 US US05/481,594 patent/US3989707A/en not_active Expired - Lifetime
1975
- 1975-04-25 PH PH17101A patent/PH13604A/en unknown
- 1975-05-14 AU AU81138/75A patent/AU500910B2/en not_active Expired
- 1975-05-15 NO NO751735A patent/NO142400C/no unknown
- 1975-05-19 FI FI751462A patent/FI59589C/fi not_active IP Right Cessation
- 1975-05-21 CA CA227,398A patent/CA1053235A/fr not_active Expired
- 1975-05-23 GB GB22512/75A patent/GB1505173A/en not_active Expired
- 1975-05-27 CS CS753693A patent/CS190480B2/cs unknown
- 1975-06-12 FR FR7518434A patent/FR2275210A1/fr active Granted
- 1975-06-18 SE SE7507026A patent/SE416298B/xx unknown
- 1975-06-19 JP JP50073830A patent/JPS5840553B2/ja not_active Expired
- 1975-06-19 HU HUJA735A patent/HU170435B/hu unknown
- 1975-06-19 DE DE2527261A patent/DE2527261C2/de not_active Expired
- 1975-06-19 BE BE157471A patent/BE830403A/xx not_active IP Right Cessation
- 1975-06-19 PL PL1975181386A patent/PL98220B1/pl unknown
- 1975-06-19 ES ES438714A patent/ES438714A1/es not_active Expired
- 1975-06-20 CH CH809875A patent/CH615173A5/de not_active IP Right Cessation
- 1975-06-20 SU SU752148462A patent/SU585811A3/ru active
- 1975-06-20 ZA ZA3968A patent/ZA753968B/xx unknown
- 1975-06-20 IE IE1381/75A patent/IE41383B1/xx unknown
- 1975-06-20 IL IL47529A patent/IL47529A/xx unknown
- 1975-06-20 DK DK281975AA patent/DK141751B/da not_active IP Right Cessation
- 1975-06-20 AT AT476175A patent/AT345833B/de not_active IP Right Cessation
- 1975-06-20 NL NLAANVRAGE7507368,A patent/NL180587C/xx not_active IP Right Cessation
- 1975-07-20 YU YU01594/75A patent/YU159475A/xx unknown
1976
- 1976-02-13 SE SE7601636A patent/SE415298B/xx unknown

Also Published As

Publication number	Publication date
ES438714A1 (es)	1977-07-01
IE41383B1 (en)	1979-12-19
ATA476175A (de)	1978-02-15
FR2275210A1 (fr)	1976-01-16
NO142400C (no)	1980-08-13
NO142400B (no)	1980-05-05
SU585811A3 (ru)	1977-12-25
NL7507368A (nl)	1975-12-23
ZA753968B (en)	1977-01-26
JPS5113780A (fr)	1976-02-03
NL180587C (nl)	1987-03-16
DK281975A (fr)	1975-12-22
PL98220B1 (pl)	1978-04-29
SE7507026L (sv)	1975-12-22
CS190480B2 (en)	1979-05-31
AU8113875A (en)	1976-11-18
US3989707A (en)	1976-11-02
FR2275210B1 (fr)	1978-12-22
DK141751B (da)	1980-06-09
PH13604A (en)	1980-08-05
DK141751C (fr)	1980-11-03
IL47529A0 (en)	1975-08-31
AT345833B (de)	1978-10-10
DE2527261A1 (de)	1976-01-08
GB1505173A (en)	1978-03-30
SE7601636L (sv)	1976-02-13
CA1053235A (fr)	1979-04-24
JPS5840553B2 (ja)	1983-09-06
NO751735L (fr)	1975-12-23
AU500910B2 (en)	1979-06-07
IL47529A (en)	1978-10-31
DE2527261C2 (de)	1986-09-04
SE416298B (sv)	1980-12-15
IE41383L (en)	1975-12-21
YU159475A (en)	1982-02-28
FI59589B (fi)	1981-05-29
NL180587B (nl)	1986-10-16
BE830403A (nl)	1975-12-19
FI751462A (fr)	1975-12-22
FI59589C (fi)	1981-09-10
SE415298B (sv)	1980-09-22
HU170435B (fr)	1977-06-28

Publication	Publication Date	Title
CH615173A5 (fr)	1980-01-15
DE2610228C2 (fr)	1990-04-05
DE2503815C2 (de)	1986-05-22	Indazol-Derivate, Verfahren zu ihrer Herstellung und Arzneimittel
DE2636614C2 (fr)	1988-04-07
DE2400094A1 (de)	1974-07-18	1-geschweifte klammer auf 1- eckige klammer auf 2-(1,4-benzodioxan-2-yl) -2-hydroxyaethyl eckige klammer zu -4-piperidyl geschweifte klammer zu -2-benzimidazolinone, verfahren zu iherer herstellung und arzneimittel
DE2322470A1 (de)	1974-11-21	Neue indolyl-piperidino-(bzw. 1,2,5,6tetrahydro-pyridyl-)butyrophenone und verfahren zu ihrer herstellung
DE602004008668T2 (de)	2008-06-12	Benzoxazinderivate und deren verwendungen
DD291323A5 (de)	1991-06-27	Verfahren zur herstellung von piperidinen
DE2645125C2 (fr)	1988-11-24
DE69531522T2 (de)	2004-06-24	Heterozyklische Verbindungen
EP0004358B1 (fr)	1982-01-06	N-oxacyclylalkylpipéridines, procédé pour leur préparation, compositions pharmaceutiques contenant ces composés
DE2651083A1 (de)	1978-05-18	Neue o-alkylierte hydroxylamine, verfahren zu ihrer herstellung und ihre verwendung
DE69513846T2 (de)	2000-07-06	N-substituierte piperidinyl bicyclische benzoatderivate
DE3851388T2 (de)	1995-01-19	Substituierte N-(3-Hydroxy-4-piperidinyl)benzamide.
CH643554A5 (de)	1984-06-15	Verfahren zur herstellung von piperidinopropanolderivaten.
EP0282502A1 (fr)	1988-09-21	Derives d'imidazole.
DE2905876A1 (de)	1980-08-28	Neue piperidinopropylderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE2628570A1 (de)	1976-12-30	10- eckige klammer auf omega- (benzoylpiperidinyl)-alkyl eckige klammer zu phenothiazine und verfahren zu ihrer herstellung
DE2642856A1 (de)	1977-03-24	N-aryl-n-(4-piperidinyl)-arylacetamide, verfahren zu ihrer herstellung und arzneimittel
DE69637412T2 (de)	2009-01-22	Prokinetisch wirksame oxadiazole
CH417574A (de)	1966-07-31	Verfahren zur Herstellung therapeutisch wirksamer Dibenzocycloheptanderivate
DE2737630A1 (de)	1979-03-01	Neue aminopropanolderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE2819873C2 (fr)	1989-05-03
DE2040231C3 (de)	1979-04-12	4-Aryl-l-(4,4-diaryl-butyl)-4hydröxypiperidine, ihre Herstellung und Verwendung
EP0266532A1 (fr)	1988-05-11	Sels d'imidazolium disubstitués 1,3

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Date	Code	Title	Description
1984-02-29	PL	Patent ceased
2024-10-31	PL	Patent ceased